The adrenergic system plays vital roles in the maintenance of normal physiological functioning. In the fetal and neonatal rat, adrenergic tissues are markedly immature in their capabilities to synthesize, store and secrete catecholamines; it is commonly observed that many drugs which act on peripheral of CNS catecholamines have markedly different effects in the immature organism, and that administration of these agents often produces permanent alterations in adrenergic function. The proposed study will examine the acute and chronic actions of morphine and methadone in adult and immature rats in the central nervous system, heart and adrenal medulla. The effects of drug exposure in utero and early in postnatal development will be contrasted with the actions in mature rats, and in addition the post-exposure developmental characteristics of catecholamine disposition will be evaluated for both drugs. The ability of tissues to synthesize and degrade catecholamines will be evaluated by measurements of tyrosine hydroxylase, dopa decarboxylase, dopamine beta-hydroxylase and monoamine oxidase activities. The amine uptake and storage capabilities of each tissue, the number of storage vesicles, and the degree to which amine stores can be mobilized during stress or depleted by drugs, will also be measured. These data will establish how the drugs alter the development of adrenergic functions as well as elucidating the differences in activity of the drugs in the immature organism. The proposed experiment will identify on the biochemical and functional scales specific loci of opiate-induced maturational defects and age-dependent differences in central and peripheral adrenergic function, and will compare the relative effects of exposure to and withdrawal after morphine vs. methadone during development.